Farnesyl Transferase Inhibitors Induce Apoptosis of Ras-transformed Cells Denied Substratum Attachment

摘要: Farnesyl transferase inhibitors (FTIs) are a novel class of antitumor drugs that block the oncogenic activity Ras. Because FTIs lack significant cell toxicity in vitro and vivo, question is how they cause tumor regression. We now report fact potent activators apoptosis Ras-transformed cells if attachment to substratum prevented. When cultured at high density or on polyHEMA, nonadherent substrate, exhibited massive DNA degradation death within 24 h treatment with FTI L-739,749. Death was p53-independent inhibited by suppressor BCL-XL. Furthermore, significantly attenuated ectopic expression farnesyl-independent form RhoB, Rho protein previously implicated as critical target for inhibition FTIs. The findings suggest link between Rho-dependent adhesion signaling. our work indicates revert state which cell-substratum necessary viability suggests forms basis drug-induced